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At least 1,153 records · Page 64Linked to original sources
PubMed1995

Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice.

The oncogene bmi-1, which was originally found to be involved in B- and T-cell lymphoma formation encodes a protein with a domain of homology to the Drosophila protein Posterior sex combs (Psc) and its relative Suppressor 2 of Zeste (Su(z)2) (refs 4 and 5). Psc is a member of the Polycomb-group gene family, which is required to maintain the repression of homeotic genes that regulate the identities of Drosophila segments. The possibility that bmi-1 may play a similar role in vertebrates was suggested by our previous finding that mice lacking the bmi-1 gene show posterior transformations of the axial skeleton. Here we report that transgenic mice overexpressing Bmi-1 protein show the opposite phenotype, namely a dose-dependent anterior transformation of vertebral identity. The anterior expression boundary of the Hoxc-5 gene is shifted in the posterior direction, indicating that Bmi-1 is involved in the repression of Hox genes. We propose that Bmi-1 is a member of a vertebrate Polycomb complex that regulates segmental identity by repressing Hox genes throughout development.

Animals↗
PubMed2003

A convergent approach to the marine natural product eleutherobin: synthesis of key intermediates and attempts to produce the basic skeleton.

Synthesis of (1R,5R,6R)-2-(6-hydroxymethyl-5-isopropyl-2-methylcyclohex-2-enyl)-N- methoxy-N-methylacetamide 8 from R-(-)-phellandrene in six steps, and (3aR*,4S*,6R*,6aS*)- (6-hydroxymethyl-4-methoxy-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol- 4-yl)acetic acid methyl ester 17 from tetrabromoacetone and 2-methoxy-5-methylfuran in six steps, provided two key fragments which have been combined to produce intermediates for attempted construction of the basic skeleton of eleutherobin.

Acetamides↗
PubMed2003

Synthesis and molecular structure of new acyclic analogues of nucleotides with a 1,2-alkadienic skeleton.

Reaction of 1-chloro-4-(diethoxyphosphonyl)alka-2,3-dienes 14,15 with purine and pyrimidine heterocyclic bases in the presence of cesium carbonate afforded new acyclic analogues of nucleotides containing a 1,2-alkadienic skeleton 18-23. Dealkylation of 18-23 furnished phosphonic acids 2a-f. In contrast, alkylation reaction with 1-chloro-4-(diethoxyphosphonyl)octa-2,3-diene 16 led to Z- and E-1,3-alkadienic phosphonates 25a,b and 26a,b. A similar reaction with 1-chloro-4-(diethoxyphosphonyl)-2-methylbuta-2,3-diene 17 led to the elimination of hydrochloride and formation of 4-(diethylphosphonyl)-2-methylbut-1-en-3-yne 24. Molecular structures of new acyclic nucleotides 18 and 2f are determined by X-ray crystallographic analysis.

Alkadienes↗
PubMed2005

Structure and anti-HIV activity of micrandilactones B and C, new nortriterpenoids possessing a unique skeleton from Schisandra micrantha.

Two new highly oxygenated nortriterpenoids with a unique norcycloartane skeleton, micrandilactones B and C, were isolated from Schisandra micrantha; micrandilactone C exhibited an EC50 value of 7.71 microg/mL (SI > 25.94) against HIV-1 replication with minimal cytotoxicity, and the potent anti-HIV-1 activity and unique structural features of make it a promising lead for therapeutic development of a new generation of anti-HIV drug.

Animals↗
PubMed1987

Concanavalin A binding to human erythrocytes leads to alterations in properties of the membrane skeleton.

Three properties related to the erythrocyte membrane skeleton are found to be altered after the binding of concanavalin A (Con A) to erythrocytes or their isolated membranes. Con A binding to normal erythrocytes imparts resistance to heat (49 degrees C)-induced fragmentation of the cells. The fragmentation, due to denaturation of spectrin at 49 degrees C, is prevented by Con A in a dose-dependent manner, but levels off at concentrations of Con A in excess of 100 micrograms/ml. The binding of Con A to ghosts isolated from normal, trypsin- or Pronase-treated cells prevents (completely or substantially) the elution of the skeletal protein complex when the membranes are extracted under low-ionic-strength conditions in the cold. The Con A-agglutinated membranes of trypsin- and Pronase-treated, but not normal, cells show cross-linking of skeletal proteins and band 3 with dimethyl adipimidate, a 0.86 nm (8.6 A)-span bifunctional reagent. The extent of cross-linking is greater in the Pronase-treated membrane than in the less-agglutinable trypsin-treated membranes. The results show that, after Con A has bound, rearrangements occur in the membrane that alter properties of the skeletal proteins. Additionally, redistribution of the skeletal proteins and the Con A receptor occurs in the lectin-agglutinated membranes.

Chromatography, Affinity↗
PubMed1978

A study of the craniofacial skeleton.

Multivariate analysis of craniofacial profiles demonstrated the complex interaction between the brain case and facial skeleton during growth and between various occlusal categories. Only by investigating craniofacial growth data still further will it be possible to establish normative standard growth patterns that can withstand critical scientific appraisal.

Adolescent↗
PubMed2000

Differential distribution of spicule matrix proteins in the sea urchin embryo skeleton.

Spicule matrix proteins are the products of primary mesenchyme cells, and are present in calcite spicules of the sea urchin embryo. To study their possible roles in skeletal morphogenesis, monoclonal antibodies against SM50, SM30 and another spicule matrix protein (29 kDa) were obtained. The distribution of these proteins in the embryo skeleton was observed by immunofluorescent staining. In addition, their distribution inside the spicules was examined by a 'spicule blot' procedure, direct immunoblotting of proteins embedded in crystallized spicules. Our observations showed that SM50 and 29 kDa proteins were enriched both outside and inside the triradiate spicules of the gastrulae, and also existed in the corresponding portions of growing spicules in later embryos and micromere cultures. The straight extensions of the triradiate spicules and thickened portions of body rods in pluteus spicules were also rich in these proteins. The SM30 protein was only faintly detected along the surface of spicules. By examination using the spicule blot procedure, however, SM30 was clearly detectable inside the body rods and postoral rods. These results indicate that SM50 and 29 kDa proteins are concentrated in radially growing portions of the spicules (normal to the c-axis of calcite), while SM30 protein is in the longitudinally growing portions (parallel to the c-axis). Such differential distribution suggests the involvement of these proteins in calcite growth during the formation of three-dimensionally branched spicules.

Animals↗
PubMed1997

Stage-specific expression patterns of alkaline phosphatase during development of the first arch skeleton in inbred C57BL/6 mouse embryos.

Timing and pattern of expression of alkaline phosphatase was examined during early differentiation of the 1st arch skeleton in inbred C57BL/6 mice. Embryos were recovered between 10 and 18 d of gestation and staged using a detailed staging table of craniofacial development prior to histochemical examination. Expression of alkaline phosphatase is initiated at stage 20.2 in the plasma membrane of mesenchymal cells in the distal region of the first arch. Expression is strongest in osteoid (unmineralised bone matrix) and presumptive periosteum at stage 21.32. Mineralisation begins at stage E23. Expression is present in the mineralised bone matrix. Secondary cartilages form in the condylar and angular processes by stage M24. The cartilaginous cells and surrounding cells in the processes are all alkaline phosphatase-positive and surrounded by the common periosteum, suggesting that progenitor cells of the processes, dentary ramus and secondary cartilages all originate from a common pool. Nonhypertrophied chondrocytes of Meckel's cartilage express alkaline phosphatase at stage M23. Expression in these chondrocytes is preceded by the expression in their adjacent perichondrium. This is true of chondrocytes in all other cranial cartilages examined. 3-D reconstruction of expression in Meckel's cartilage also revealed that the chondrocytes of Meckel's cartilage which express alkaline phosphatase and the matrix of which undergoes mineralisation are those surrounded by the alkaline phosphatase-positive dentary ramus. By stage 25, coincident with mineralisation in the distal section of Meckel's cartilage, most chondrocytes are strongly positive. The perichondria of malleus and incus cartilages express alkaline phosphatase at stage M24. Nonhypertrophied chondrocytes along these perichondria also express alkaline phosphatase. Superficial and deep cells in the dental laminae of incisor and 1st molar teeth become alkaline phosphatase-positive at the bud stage, stages 21.16 and 21.32, respectively. Dental papillae are negative until stage M24 when alkaline phosphatase expression begins in the dental papillae and follicles of the incisor teeth and the dental follicles of the 1st molar teeth. The dental papillae of the 1st molar teeth express alkaline phosphatase at stage 25. Expression in the dental papillae and follicles appears to coincide with cellular differentiation of follicle from papilla. The presumptive squamosal, ectotympanic and gonial membrane bones, lingual oral epithelial cells connected to the dental laminae of the incisor teeth, hair follicle papillae and sheath and surrounding dermis all express alkaline phosphatase in a stage-specific manner.

Alkaline Phosphatase↗
PubMed1997

An immunocytochemical study of changes in the human erythrocyte membrane skeleton produced by stretching examined by the quick-freezing and deep-etching method.

A quick-freezing and deep-etching method in combination with erythrocyte splitting was used to examine the cytoplasmic aspect of whole-mount human erythrocyte membranes. Various external forces induced alterations in membrane skeletal organisation during the splitting procedure. The initial change was elongation in the peripheral part of the membrane skeleton, examined by immunostaining with a monoclonal antispectrin antibody. Under severe stretching conditions, a linear rearrangement of filamentous components was evident; these were disposed parallel to the rim of the erythrocyte, while the central part of the concavity exhibited a more compacted structure. These changes resulted in a different distribution of membrane skeletal components between central rigid and peripheral flexible areas in biconcave erythrocytes. It is suggested that the reversible membrane skeletal changes in the flexible areas which resist the external forces are important for maintaining the normal framework of biconcave human erythrocytes.

Antibodies, Monoclonal↗
PubMed2002

A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton.

This study examines interpopulation variations in the facial skeleton of 10 modern human populations and places these in an ontogenetic perspective. It aims to establish the extent to which the distinctive features of adult representatives of these populations are present in the early post natal period and to what extent population differences in ontogenetic scaling and allometric trajectories contribute to distinct facial forms. The analyses utilize configurations of facial landmarks and are carried out using geometric morphometric methods. The results of this study show that modern human populations can be distinguished based on facial shape alone, irrespective of age or sex, indicating the early presence of differences. Additionally, some populations have statistically distinct facial ontogenetic trajectories that lead to the development of further differences later in ontogeny. We conclude that population-specific facial morphologies develop principally through distinctions in facial shape probably already present at birth and further accentuated and modified to variable degrees during growth. These findings raise interesting questions regarding the plasticity of facial growth patterns in modern humans. Further, they have important implications in relation to the study of growth in the face of fossil hominins and in relation to the possibility of developing effective discriminant functions for the identification of population affinities of immature facial skeletal material. Such tools would be of value in archaeological, forensic and anthropological applications. The findings of this study underline the need to examine more deeply, and in more detail, the ontogenetic basis of other causes of craniometric variation, such as sexual dimorphism and hominin species differentiation.

Adolescent↗
PubMed1984

The effect of short and skeleton long photoperiods on the plasma concentrations of prolactin and cortisol in sheep.

Suffolk-cross lambs, aged eight weeks, were exposed to either short photoperiods (8L : 16D, SP; 7 castrated males and 6 females) or skeleton long photoperiods (7L : 10D : 1L : 6D, SLP; 6 castrated males and 7 females). They were fed individually on a complete pelleted diet at 70 g/kg live weight 0.75/day. Blood samples were taken monthly by jugular puncture for three months and, after 39 days on experiment, jugular catheters were inserted for frequent sampling over a 24 h period. The samples were assayed for prolactin using radioimmunoassay and for cortisol by competitive protein binding. SLP caused a large and significant increase in plasma prolactin throughout the experiment, with no effect on sex. During the 24 h period there were consistent peaks of prolactin at the start of both dark phases under SLP, with lower levels around the start of both light phases; under SP, prolactin tended to be higher in the middle of the light phase and the middle of the dark phase than at other times. Considerable hourly fluctuations were observed in cortisol levels but an obvious 24 h rhythm was not. Mean levels were, however, significantly higher under SP (38.3 nmol/l) than under SLP (26.8 nmol/l).

Animals↗
PubMed2000

The effect of chemotherapy on the growing skeleton.

With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age.

Adult↗
PubMed2003

The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton.

AIM: To establish the effect of three single chemotherapeutic agents on the growing skeleton, male Wistar rats were studied. METHODS: From the age of 4 weeks the rats were given iv doxorubicin (DOX) 15 mg/m(2) body surface area (BSA), methotrexate (MTX) 60 mg/m(2) BSA or cisplatin (CDDP) 7.5 mg/m(2) BSA. One non-treated control group was fed ad libitum (ad lib) and for every drug-treated group there was a diet-control group. After dissection at 13 weeks of age, morphology of the proximal tibial growth plate and metaphysis were studied. RESULTS: Compared to the ad lib group, DOX significantly decreased and MTX increased growth plate height (P<0.05). CDDP decreased height of the proliferating layer (P<0.05). Trabecular volume was decreased in the DOX and CDDP treated rats compared to the ad lib group (P=0.054). Compared to the diet control group trabecular bone volume was unaffected in the DOX group and decreased in the MTX and CDDP group (P<0.05). CONCLUSIONS: Doxorubicin causes growth plate thinning, methotrexate increases growth plate height and cisplatin does not affect growth plate height. All three chemotherapeutic agents decrease the trabecular volume of the proximal tibial metaphysis. Part of the effect of DOX, MTX and CDDP is related to the treatment induced malnutrition.

Animals↗
PubMed1979

[Computer tomography of the facial skeleton and pharyngeal space (author's transl)].

Seventy-five patients with histologically confirmed abnormalities of the facial skeleton and pharynx, including the mouth and base of the tongue, were examined by computer tomography. The advantages of simultaneous demonstration of the soft tissues and bones in localised space-occupying lesions are pointed out. Accurate comparison between pre-operative descriptions and findings at operation in 30 cases showed high diagnostic accuracy. Conventional, multi-dimensional film tomography is being increasingly replaced by computer tomography.

Diagnosis, Differential↗